Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: HNRNPR

Gene summary for HNRNPR

Gene summary.

Gene information	Species	Human
	Gene symbol	HNRNPR
	Gene ID	10236
	Gene name	heterogeneous nuclear ribonucleoprotein R
	Gene Alias	HNRPR
	Cytomap	1p36.12
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	Q0VGD6

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
10236	HNRNPR	HTA11_3410_2000001011	Human	Colorectum	AD	4.73e-04	-3.71e-01	0.0155
10236	HNRNPR	HTA11_99999965104_69814	Human	Colorectum	MSS	1.42e-09	7.10e-01	0.281
10236	HNRNPR	A015-C-203	Human	Colorectum	FAP	2.58e-25	-2.22e-01	-0.1294
10236	HNRNPR	A015-C-204	Human	Colorectum	FAP	2.33e-03	-1.27e-01	-0.0228
10236	HNRNPR	A002-C-201	Human	Colorectum	FAP	2.57e-06	-1.68e-01	0.0324
10236	HNRNPR	A002-C-203	Human	Colorectum	FAP	4.98e-03	-1.23e-01	0.2786
10236	HNRNPR	A001-C-108	Human	Colorectum	FAP	2.34e-15	-8.93e-02	-0.0272
10236	HNRNPR	A002-C-205	Human	Colorectum	FAP	2.20e-14	-1.34e-01	-0.1236
10236	HNRNPR	A015-C-006	Human	Colorectum	FAP	4.75e-13	1.81e-01	-0.0994
10236	HNRNPR	A015-C-106	Human	Colorectum	FAP	3.26e-09	-1.42e-01	-0.0511
10236	HNRNPR	A002-C-114	Human	Colorectum	FAP	1.62e-11	-2.18e-01	-0.1561
10236	HNRNPR	A015-C-104	Human	Colorectum	FAP	3.76e-27	-1.00e-01	-0.1899
10236	HNRNPR	A001-C-014	Human	Colorectum	FAP	4.05e-11	-6.85e-02	0.0135
10236	HNRNPR	A002-C-016	Human	Colorectum	FAP	7.47e-16	-1.93e-01	0.0521
10236	HNRNPR	A015-C-002	Human	Colorectum	FAP	2.27e-07	-1.95e-01	-0.0763
10236	HNRNPR	A001-C-203	Human	Colorectum	FAP	1.05e-05	2.28e-02	-0.0481
10236	HNRNPR	A002-C-116	Human	Colorectum	FAP	4.47e-24	-1.35e-01	-0.0452
10236	HNRNPR	A014-C-008	Human	Colorectum	FAP	3.30e-09	3.21e-02	-0.191
10236	HNRNPR	A018-E-020	Human	Colorectum	FAP	7.97e-13	-2.10e-01	-0.2034
10236	HNRNPR	F034	Human	Colorectum	FAP	3.61e-13	9.08e-03	-0.0665

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:0046700110	Skin	cSCC	heterocycle catabolic process	178/4864	445/18723	4.45e-11	2.13e-09	178
GO:0044270110	Skin	cSCC	cellular nitrogen compound catabolic process	179/4864	451/18723	8.34e-11	3.79e-09	179
GO:0019439110	Skin	cSCC	aromatic compound catabolic process	183/4864	467/18723	1.76e-10	7.68e-09	183
GO:0061013110	Skin	cSCC	regulation of mRNA catabolic process	79/4864	166/18723	1.57e-09	5.92e-08	79
GO:1901361110	Skin	cSCC	organic cyclic compound catabolic process	188/4864	495/18723	1.92e-09	7.01e-08	188
GO:0043487110	Skin	cSCC	regulation of RNA stability	80/4864	170/18723	2.39e-09	8.52e-08	80
GO:004348824	Skin	cSCC	regulation of mRNA stability	75/4864	158/18723	4.64e-09	1.55e-07	75
GO:000762323	Skin	cSCC	circadian rhythm	89/4864	210/18723	1.55e-07	3.51e-06	89
GO:006115718	Skin	cSCC	mRNA destabilization	44/4864	84/18723	2.14e-07	4.60e-06	44
GO:006101418	Skin	cSCC	positive regulation of mRNA catabolic process	45/4864	87/18723	2.53e-07	5.29e-06	45
GO:005077918	Skin	cSCC	RNA destabilization	44/4864	88/18723	1.16e-06	2.03e-05	44
GO:003424915	Skin	cSCC	negative regulation of cellular amide metabolic process	104/4864	273/18723	6.44e-06	9.00e-05	104
GO:004851123	Skin	cSCC	rhythmic process	110/4864	298/18723	1.83e-05	2.19e-04	110
GO:001714814	Skin	cSCC	negative regulation of translation	93/4864	245/18723	2.28e-05	2.63e-04	93
GO:0008380113	Thyroid	PTC	RNA splicing	273/5968	434/18723	4.44e-41	1.40e-37	273
GO:0009896113	Thyroid	PTC	positive regulation of catabolic process	278/5968	492/18723	3.35e-30	2.64e-27	278
GO:0031331113	Thyroid	PTC	positive regulation of cellular catabolic process	249/5968	427/18723	5.28e-30	3.58e-27	249
GO:0000375113	Thyroid	PTC	RNA splicing, via transesterification reactions	202/5968	324/18723	6.81e-30	3.91e-27	202
GO:0000377113	Thyroid	PTC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	199/5968	320/18723	2.96e-29	1.44e-26	199
GO:0000398113	Thyroid	PTC	mRNA splicing, via spliceosome	199/5968	320/18723	2.96e-29	1.44e-26	199

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

HNRNPR

SNV

Missense_Mutation

novel

c.565G>A

p.Gly189Arg

p.G189R

O43390

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HNRNPR

SNV

Missense_Mutation

rs754424759

c.694N>T

p.Arg232Cys

p.R232C

O43390

protein_coding

deleterious(0.02)

probably_damaging(0.997)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HNRNPR

SNV

Missense_Mutation

c.511N>C

p.Lys171Gln

p.K171Q

O43390

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-BH-A0C3-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HNRNPR

SNV

Missense_Mutation

c.1366N>T

p.Gly456Trp

p.G456W

O43390

protein_coding

tolerated(0.12)

probably_damaging(0.943)

TCGA-E2-A15J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

HNRNPR

insertion

Frame_Shift_Ins

novel

c.271_272insACCGGAAGGAGGCAGACATCATGATCTTTTTTGCTTCTGGT

p.Val91AspfsTer26

p.V91Dfs*26

O43390

protein_coding

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HNRNPR

SNV

Missense_Mutation

c.139N>C

p.Asp47His

p.D47H

O43390

protein_coding

deleterious(0.03)

possibly_damaging(0.614)

TCGA-EK-A2H0-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HNRNPR

SNV

Missense_Mutation

c.1096N>A

p.Glu366Lys

p.E366K

O43390

protein_coding

tolerated(0.25)

benign(0.219)

TCGA-FU-A3HY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HNRNPR

SNV

Missense_Mutation

novel

c.790N>A

p.Glu264Lys

p.E264K

O43390

protein_coding

tolerated(0.07)

probably_damaging(0.967)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HNRNPR

SNV

Missense_Mutation

c.610N>G

p.Gln204Glu

p.Q204E

O43390

protein_coding

tolerated(0.85)

possibly_damaging(0.693)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HNRNPR

SNV

Missense_Mutation

novel

c.454C>T

p.Pro152Ser

p.P152S

O43390

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-MA-AA42-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID

Symbol

Category

Interaction Types

Drug Claim Name

Drug Name

PMIDs

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